TY - JOUR
T1 - Risk of Neuropsychiatric Adverse Events Associated with Varenicline Treatment for Smoking Cessation among Dutch Population
T2 - A Sequence Symmetry Analysis
AU - Wang, Yuanyuan
AU - van Boven, Job F M
AU - Bos, Jens H J
AU - Schuiling-Veninga, Catharina C M
AU - Boezen, H Marike
AU - Wilffert, Bob
AU - Hak, Eelko
N1 - Funding Information:
The authors would like to thank IADB.nl pharmacies for generous contributions of providing their data for research. This study was supported by internal funding from University of Groningen, The Netherlands. Yuanyuan Wang obtained a scholarship (file number: 201506010259) from the China Scholarship Council (CSC, http://www.csc.edu.cn/ ) for her PhD study The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
China Scholarship Council, Grant/Award Number: 201506010259; University of Groningen, The Netherlands Funding information
Publisher Copyright:
© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.
PY - 2022/2
Y1 - 2022/2
N2 - Purpose: Varenicline is an effective treatment for smoking cessation. While clinical trials did not confirm a causal role, case reports suggested a possible link of varenicline with neuropsychiatric adverse drug events (NPAEs). This study aims to investigate the risk of NPAEs associated with varenicline initiation among the general population in a real-world setting. Methods: We conducted a sequence symmetry analysis (SSA) based on the University of Groningen IADB.nl prescription database. We selected incident users of both varenicline and marker drugs for NPAEs, including depression, anxiety and sleep disorder within different time-intervals. Adjusted sequence ratios (aSR) were calculated for each time-interval. Results: Within 365-days' time-interval 1066 patients were incident users of both varenicline and NPAE marker drugs. In total, 505 patients were prescribed varenicline before NPAE marker drugs and 561 vice versa (crude sequence ratio [cSR] 0.90, 95% CI: 0.80–1.02). After adjustments for trends in prescriptions, overall a null association was found (aSR 1.00, 95% CI: 0.89–1.13). Regarding specific NPAEs, no increased risks were found for depression nor anxiety within any time-interval. A small transient increased risk was found for sleep disorders, particularly in earlier time-intervals 3 and 6 months (aSRs 1.52, 95% CI: 1.10–2.11 and 1.45, 95% CI: 1.15–1.83, respectively). Subgroup and sensitivity analyses showed similar findings. Conclusions: Varenicline initiation was unlikely to be associated with an increased risk of taking anti-depressants nor anti-anxiety drugs. Yet a small, but statistically significant, transient association with drugs for sleep disorders was noticed, possibly associated with withdrawal symptoms caused by smoking cessation.
AB - Purpose: Varenicline is an effective treatment for smoking cessation. While clinical trials did not confirm a causal role, case reports suggested a possible link of varenicline with neuropsychiatric adverse drug events (NPAEs). This study aims to investigate the risk of NPAEs associated with varenicline initiation among the general population in a real-world setting. Methods: We conducted a sequence symmetry analysis (SSA) based on the University of Groningen IADB.nl prescription database. We selected incident users of both varenicline and marker drugs for NPAEs, including depression, anxiety and sleep disorder within different time-intervals. Adjusted sequence ratios (aSR) were calculated for each time-interval. Results: Within 365-days' time-interval 1066 patients were incident users of both varenicline and NPAE marker drugs. In total, 505 patients were prescribed varenicline before NPAE marker drugs and 561 vice versa (crude sequence ratio [cSR] 0.90, 95% CI: 0.80–1.02). After adjustments for trends in prescriptions, overall a null association was found (aSR 1.00, 95% CI: 0.89–1.13). Regarding specific NPAEs, no increased risks were found for depression nor anxiety within any time-interval. A small transient increased risk was found for sleep disorders, particularly in earlier time-intervals 3 and 6 months (aSRs 1.52, 95% CI: 1.10–2.11 and 1.45, 95% CI: 1.15–1.83, respectively). Subgroup and sensitivity analyses showed similar findings. Conclusions: Varenicline initiation was unlikely to be associated with an increased risk of taking anti-depressants nor anti-anxiety drugs. Yet a small, but statistically significant, transient association with drugs for sleep disorders was noticed, possibly associated with withdrawal symptoms caused by smoking cessation.
KW - smoking cessation
KW - VARENICLINE
U2 - 10.1002/pds.5351
DO - 10.1002/pds.5351
M3 - Article
C2 - 34464494
SN - 1053-8569
VL - 31
SP - 158
EP - 166
JO - Pharmacoepidemiology and Drug Safety
JF - Pharmacoepidemiology and Drug Safety
IS - 2
ER -